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TISSUE-SPECIFIC STEM CELLS

Bone Marrow Multipotent Mesenchymal Stromal Cells Do Not Reduce Fibrosis or Improve Function in a Rat Model of Severe Chronic Liver Injury

^aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,
^bHospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,
^cDepartamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Key Words. Mesenchymal stromal cells • Bone marrow • Liver • Fibrosis

Correspondence: Regina Coeli dos Santos Goldenberg, Ph.D., Avenida Carlos Chagas Filho, 373, Edifício do Centro de Ciências da Saúde, Bloco G (Instituto de Biofísica Carlos Chagas Filho), 2° andar/sala 53, Cidade Universitária 21941-902 Rio de Janeiro, Brazil. Telephone: +55 21 25626559; Fax: +55 21 22808193; e-mail: rcoeli{at}biof.ufrj.br

Received November 8, 2007; accepted for publication February 19, 2008.
First published online in STEM CELLS EXPRESS   February 28, 2008.



The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 x 10⁷ cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury.

Disclosure of potential conflicts of interest is found at the end of this article.